Protective effects of Lonicerae Japonicae Flos against acute alcoholic liver injury in rats based on network pharmacology / 中国中药杂志

This study aims to explore underlying mechanism of Lonicerae Japonicae Flos(LJF) in protecting rats against acute alcoholic liver injury(ALI) based on mitogen-activated protein kinase(MAPK) pathway. First, the targets of LJF in preventing ALI were predicted by network pharmacology and the component-target-pathway network was constructed, so that the key targets of LJF components acting on MAPK pathway were screened. Second, male SD rats were randomized into the control(KB) group, model(MX) group, positive(YX) group, and LJF high-(GJ), medium-(ZJ), and low-(DJ) dose groups. Each administration group was given(ig) corresponding drugs for 7 days and KB group and MX group received(ig) equal volume of distilled water every day. Except for KB group, rats were given Chinese spirit(56%, 3 days) for ALI modeling. The levels of aspartate transaminase(AST), alanine transaminase(ALT), interleukin-6(IL6) and tumor necrosis factor-α(TNF-α) in serum and malondialdehyde(MDA), glutathione(GSH), superoxide dismutase(SOD) and glutathione peroxidase(GSH-Px) in liver tissue of rats in each group were detected. Furthermore, we employed quantitative real-time PCR(qRT-PCR) to probe the effects of LJF on the key targets of MAPK pathway in ALI rats. A total of 28 active components of LJF were screened from TCMSP database, and 317 intersected with ALI-related targets. According to Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis, the 317 targets involved 226 pathways, which were mainly liver disease, inflammation, immunity, apoptosis and other related pathways. According to the MAPK pathway-target-active component network, the key active components of LJF, such as chlorogenic acid, hederagenol, and hyperoside, acted on 25 key targets of MAPK pathway. The results of in vivo experiments showed decreased levels of AST, ALT, and MDA in DJ, ZJ, and GJ groups(P<0.01 or P<0.05), reduced levels of IL6 in DJ and GJ groups(P<0.01 or P<0.05), and improved levels of SOD and GSH in ZJ and GJ groups(P<0.01 or P<0.05). The results of qRT-PCR demonstrated that the expression levels of mitogen-activated protein kinase kinase 4(MAPK2 K4) and mitogen-activated protein kinase 3(MAPK3) were decreased in DJ, ZJ, and GJ groups(P<0.01). The network pharmacology and experimental verification showed that the active components in LJF can reduce the inflammatory factor level and enhance the activities of SOD and GSH-Px by inhibiting the expression of key targets of MAPK pathway, thus alleviating and preventing liver damage caused by alcohol.

Observation on effect of peg interferon lphaa-2a treating lamivudine resistant chronic hepatitis B / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To observe the efficacy and safety of PEG-interferon alpha-2a (PEG-IFNalpha-2a) treatment on lamivudine (LAM)-resistant chronic hepatitis B (CHB) patients.</p><p><b>METHODS</b>Eighty-one patients with lamivudine-resistant HBeAg (+) chronic hepatitis B patients were enrolled and divided into PEG-IFNalpha-2a treatment group (40 cases) and adefovir dipivoxil (ADV) control group (41 cases). Two groups were combined with LAM in the first 12 weeks(w). The ALT normalization rate, the HBV DNA and HBeAg negative rate, and the HBeAg seroconversion rate were observed in 12 W, 24 W, 48 W.</p><p><b>RESULTS</b>The ALT normalization rate in 12 W, 24 W of PEG-IFNalpha-2a group was 62.5% and 80.0%. And it was higher than that of ADV group. The HBeAg negative rate and HBeAg seroconversion rate in 48 W of PEG-IFNalpha-2a group were 60% and 57.5% , which were higher than that of ADV group. The difference was statistically significant (P < 0.05).</p><p><b>CONCLUSION</b>PEG-IFNalpha-2a treatment of lamivudine-resistant HBeAg (+) chronic hepatitis B is superior to ADV, and its security is well.</p>

Liver support therapy with molecular adsorbents recirculating system in liver failure: a summary of 252 cases from 14 centers in China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>A liver support therapy, named molecular adsorbents recirculating system (MARS), has been used for more than 700 liver failure patients in China. We made here a summary to evaluate the effects of MARS treatment in different applications with emphasis on hepatitis B virus (HBV) based liver failure.</p><p><b>METHODS</b>This report analyzed data of 252 patients (mean age (44.9+/- 12.7) years) in three groups: acute severe hepatitis (ASH), subacute severe hepatitis (SSH) and chronic severe hepatitis (CSH). The largest group was CSH (156 patients, 61.9%), and 188 patients (74.6%, 188/252) were infected with HBV.</p><p><b>RESULTS</b>MARS treatments were associated with significant reduction of albumin bound toxins and water-soluble toxins. Most of the patients showed a positive response with a significant improvement of multiple organ function substantiated by a significant increase in prothrombin time activity (PTA) and median arterial pressure (MAP). There was a decrease in hepatic encephalopathy (HE) grade and Child-Turcotte-Pugh (CTP) scale. Thirty-nine of 188 HBV patients (20.7%) dropped out of the commendatory consecutive therapy ending with lower survival of 43.6% while the rest of the 149 patients had a survival rate of 62.4%. Survival within the ASH and SSH groups were 81.2% and 75.0%, respectively. In the CSH group, end stage patients were predominant (65/151, 43%), whereas the early and middle stage patients had a better prognosis: early stage survival, including orthotopic liver transplantation (OLT) survival of 91.7%, middle stage survival of 75%, end stage survival of 33.8%.</p><p><b>CONCLUSIONS</b>MARS continues to be the most favorable extracorporeal treatment for liver support therapy in China for a wide range of conditions, including the majority of hepatitis B related liver failure conditions. The appropriate application of MARS for the right indications and stage of hepatic failure, as well as the fulfillment of prescribed treatments, will lead to the optimal therapeutic result.</p>

Observation on hybrid bioartificial liver support systems in treating chronic severe hepatitis: a study of 60 cases / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study the clinical efficacy of three kinds of hybrid bioartificial liver support systems (HBLSS) in treating chronic severe hepatitis.</p><p><b>METHODS</b>A bioartificial liver support system (BAL), comprising porcine hepatocytes and fiber tube style bioreactor, was constructed. Then three kinds of HBLSS were constructed: Molecular absorbent recirculating system (MARS) plus BAL; slow plasma exchange (SPE) plus continuous hemodiafiltration (CHDF) and BAL; and SPE plus hemoperfusion (HP) and BAL. One hundred-twenty patients in middle or late stages of chronic severe hepatitis were enrolled in this study. They were randomly divided into 6 groups: H1 group was treated with BAL+MARS, H2 with BAL+SPE+CHDF and H3 with BAL+SPE+HP (as treatment groups); C1 group was treated with MARS, C2 with SPE+CHDF and C3 with SPE+HP (as control groups). The changes in the clinical symptoms, in the hepatic encephalopathy stages, and in the serum total bilirubin (TBIL), the serum albumin (ALB), the prothrombin activities (PTA), endotoxin, ammonia, creatinine and a-fetal protein (AFP) were all observed before the treatment, right after it and 72 hours later. The improving and curing rates and the rates of side effect occurrences in each group were observed.</p><p><b>RESULTS</b>In all 6 groups, the patients' clinical symptoms ameliorated; their TBIL, endotoxin and ammonia levels decreased (P<0.05), and their PTA and AFP levels lowered significantly (P<0.05). But in the H1, H2 and H3 groups they were more distinctive than in the control groups. In H1 and H2 groups creatinine and ammonia levels were decreased more significantly than in the H3 group (P<0.05). The improving and curing rates of each group were 65 % (13/20), 60% (12/20), 45% (9/20), 45% (9/20), 40% (8/20) and 20% (4/20) respectively. No serious side effects were observed during the treatment.</p><p><b>CONCLUSION</b>In treating middle and late stage chronic severe hepatitis, the measures used in H1, H2 and H3 are better than those in C1, C2 and C3. Furthermore, H1 and H2 treatments can ameliorate hepatic and renal functions, prevent the development of multiple organ dysfunction syndrome, and are better than those used in H3.</p>